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Heart attack and acute coronary syndrome

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of heart attack.

Alternative Names

Acute coronary syndrome; Myocardial infarction

Medications

Thrombolytic, also called clot-busting or fibrinolytic, drugs are now mainstays in the early treatment of many patients with heart attacks. These drugs dissolve the clot, or thrombus, responsible for causing artery blockage and heart-muscle tissue death.

Specific Thrombolytics

The standard thrombolytic drugs are recombinant tissue plasminogen activators or rt-PAs. They include alteplase (Activase and reteplase (Retavase). Both are similar in effectiveness, although reteplase is easier to administer. Tenecteplase (TNKase), a newer drug, can be delivered more rapidly than alteplase, and to date, survival rates are similar. Streptokinase (Kabikinase, Streptase) is sometimes used but is somewhat less effective that the others.

Thrombolytic Administration

The sooner that thrombolytic drugs are given after a heart attack, the better. The benefits of thrombolytics are highest within the first 3 hours. They can still help if given within 12 hours of a heart attack.

A thrombolytic drug, such as alteplase or tenecteplase, is typically given by IV along with heparin, an anticoagulant drug. (Heparin, like aspirin, cannot destroy existing blood clots but can prevent clots from reforming after they are broken up.) Enoproxin, a form of heparin called low-molecular weight heparin, may be more beneficial than standard heparin.

Other anticlotting drugs are being tested in combination with thrombolytic drugs for emergency treatment following a severe heart attack. Several 2005 studies have indicated that the antiplatelet drug clopidogrel (Plavix) can help prevent arteries from reclosing, and a second heart attack, when given along with aspirin and thrombolytic drugs. The studies evaluated patients who received thrombolytic drugs for treatment of STEMI (severe heart attacks with complete artery blockage.)

Complications

Hemorrhagic stroke, usually occurring during the first day, is the most serious complication of thrombolytic therapy, but fortunately it is rare. Streptokinase given without heparin poses the lowest risk (although it is also less effective than other regimens in restoring blood flow). In general, the mortality rate from bleeding is only 3 in every 1,000 patients treated with thrombolytics, whereas 39 patients out of 1,000 would die without these clot-busting drugs. Recent evidence suggests that the survival benefits of thrombolytic therapy, particularly in combination with aspirin, last for years.

Aspirin and Other Anti-Clotting Drugs

Anticlotting drugs that prevent or break up blood clots are used at every stage of heart disease. They are generally either antiplatelets or anticoagulants. Investigators are also studying combinations of anticlotting drugs, which may be useful in patients with severe heart disease. All anticlotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

Anti-platelet Drugs. These drugs prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood-clotting.

• Aspirin. Aspirin is an antiplatelet drug. It is the most common anti-clotting drug and nearly anyone with heart disease is advised to take it daily in low dose.
• Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are powerful antiplatelet drugs that are taken by mouth.
• Glycoprotein IIb/IIIa Inhibitors. These powerful blood-thinning drugs include abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used with angioplasty and stent placement. They are proving to be helpful for ACS patients with NSTEMI (non ST-segment elevation myocardial infarction).

Anticoagulants. Anticoagulants thin blood. They include:

• Heparin
• Fondaparinux (Arixtra)
• Warfarin (Coumadin)
• Direct thrombin inhibitors such as argatroban (Novastan), danaparoid (Orgaran), and lepirudin (Refludan)

How Anti-Clotting Drugs Are Used For Heart Attacks. Unlike the thrombolytic (clot-busting) drugs, which are used to break up blood clots during a heart attack, anti-clotting drugs are used to prevent blood clots from forming in the first place. Such drugs are sometimes used along with thrombolytics, immediately after a heart attack, and also as on-going maintenance to prevent a heart attack.

• Aspirin is given immediately, and heparin is usually started during or at the end of the thrombolytic infusion.
• Clopidogrel (Plavix) is given along with aspirin, heparin, and thrombolytic (“clot busting”) drugs as emergency treatment following a heart attack and to prepare for angioplasty surgery. Clopidogrel is also beneficial for patients with acute coronary syndrome. A 2006 study suggested that clopidogrel plus aspirin may not work better than aspirin alone in preventing a first heart attack. However, many studies show that clopidogrel is an important treatment for patients who have already had a heart attack. Clopidogrel and aspirin may reduce the risk of a second heart attack by 30%. The drug combination is also recommended for patients who need angioplasty surgery and stenting.

All of these drugs pose a risk for bleeding.

Beta-Blockers

Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering pressure in the arteries. They are effective for reducing deaths from heart disease. These drugs include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc).

Administration During a Heart Attack. The beta-blocker metoprolol is given through an IV within the first few hours of a heart attack to reduce the destruction of heart tissue. However, a study suggests that emergency intravenous use of metoprolol may increase the risk of cardiac shock.

Prevention After a Heart Attack. Beta-blockers taken by mouth are also used on a long-term basis (“maintenance therapy”) after a first heart attack to help prevent future heart attacks.

Side Effects. Beta-blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good” cholesterol). Beta-blockers are categorized as non-selective or selective. Non-selective beta-blockers such as carvedilol and propranolol can narrow bronchial airways. These beta-blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

Patients should not abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may want the patient to slowly decrease the dose before stopping completely.

Statins and Other Cholesterol and Lipid-Lowering Drugs

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risk of heart disease. Several different types of drugs (statins, bile-acid binding resins, niacin, and fibrates) are used to treat cholesterol. [For more information, see In-Depth Report #23: Cholesterol.]

Statins are among the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.

Research continues to suggest that aggressive cholesterol-lowering treatment with statins can help prevent heart attacks and sudden death from heart disease. An important 2006 study found that high-dose statin treatment may even have the potential to reverse coronary artery disease.

Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.

Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors are important drugs for treating patients who have had a heart attack, particularly for patients at risk for heart failure. These drugs are commonly used to treat hypertension and are recommended as first-line treatment for people with diabetes and kidney damage.

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitor together is safe.

Magnesium

Magnesium has blood-thinning properties and may help open blood vessels. It is important to correct any magnesium deficiencies in patients (such as those who are taking diuretics).

Infection-Fighting Medications

Flu Shots. Influenza vaccinations may help protect patients against another heart attack during flu season.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae . Results from several recent large-scale clinical trials, published in 2003 in the Journal of the American Medical Association ( JAMA ) and presented in 2004 at the European Society of Cardiology annual meeting, suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.

• Review Date: 4/15/2006
• Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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